Ofloxacin is known as a quinolone series synthetic antibacterial agent having a wide antibacterial spectrum and high safety. Ofloxacin, as shown from its chemical structure, has an asymmetric carbon atom at the 3-position of the oxazine ring and includes two enantiomers, i.e., (R) isomer, and (S) isomer. In comparison of antibacterial activity between the (R) isomer and the (S) isomer, the antibacterial activity of the (S) isomer is 8 to 128 times that of the (R) isomer and, what is more, the (S) isomer is less toxic than the (R) isomer. Accordingly, the (S) isomer of ofloxacin, i.e., 3-(S)-9fluro-2,3-dihydro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-7H-pyr ido[1,2,3-de]-1,4-benzoxazine-6-carboxylic acid, is especially useful as a synthetic antibacterial agent (Farumashia, 25, 322 (1989)).
The present inventors studied a method for the production of the (S) isomer of ofloxacin. As a result, they found a method wherein optically active 2-(tetrahydropyran-2-yloxy)-1-propanol is used as an intermediate and applied a patent application (JP-A-2-732; the term "JP-A" as used herein means as an "unexamined published Japanese patent application").
As a method for producing optically active 2-(tetrahydropyran-2-yloxy)-1-propanol, there is known a method in which optically active lactic acid or an ester thereof as a raw material is reacted with 3,4-dihydro-2H-pyran in the presence of an acid catalyst, to form an optically active 2-(tetrahydropyran-2-yloxy)propionic acid ester which is then reduced with lithium aluminum hydride (Robert G. Ghirardelli, J. Am. Chem. Soc., 95, 4987(1973)).
However, not only is an (R)-lactic acid ester which is required for producing 2-(R)-(tetrahydropyran-2-yloxy)-1-propanol as an intermediate for synthesis of the (S) isomer of ofloxacin according to the method disclosed in the above-cited literature more expensive than an optically active (S) lactic acid ester, but lithium aluminum hydride used as the reducing agent is also expensive.
Accordingly, development of an economically and industrially useful, novel process for production of 2-(R)-(tetrahydropyran-2-yloxy)-1-propanol has been keenly demanded.
In the light of the situation described above, the present inventors have studied how to solve the above-mentioned drawbacks. As a result, it has been found that optically active 2-(tetrahydropyran-2-yloxy)-1-propanol having high optical purity can be obtained commercially advantageously by the use of an easily available, optically active 1-acyloxy-2-propanol through a simple operation, leading to accomplishment of the present invention.